HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 2, 1007-1015, January 14, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/2/1007    most recent M403628200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Söderberg, L. Articles by Näslund, J. Search for Related Content PubMed PubMed Citation Articles by Söderberg, L. Articles by Näslund, J. Social Bookmarking                      What's this?

Characterization of the Alzheimer's Disease-associated CLAC Protein and Identification of an Amyloid -Peptide-binding Site^*

Linda Söderberg, Hiroyoshi Kakuyama, Anna Möller, Akira Ito¶, Bengt Winblad, Lars O. Tjernberg, and Jan Näslund

From the Karolinska Institutet and Sumitomo Pharmaceuticals Alzheimer Center, Neurotec, Novum, SE-141 57 Huddinge, Sweden and the ^¶Sumitomo Pharmaceuticals Research Center, Osaka 554-0022, Japan

Amyloid -peptide (A) deposition into amyloid plaques is one of the invariant neuropathological features of Alzheimer's disease. Other proteins co-deposit with A in plaques, and one recently identified amyloid-associated protein is the collagen-like Alzheimer amyloid plaque component CLAC. It is not known how CLAC deposition affects A plaque genesis and the progress of the disease. Here, we studied the in vitro properties of CLAC purified from a mammalian expression system. CLAC displays features characteristic of a collagen protein, e.g. it forms a partly protease-resistant triple-helical structure, exhibits an intermediate affinity for heparin, and is glycosylated. Purified CLAC was also used to investigate the interaction between CLAC and A. Using a solid-phase binding assay, we show that CLAC bound with a similar affinity to aggregates formed by A-(1–40) and A-(1–42) and that the interaction was impaired by increasing salt concentrations. An 8-residue-long sequence located in non-collagenous domain 2 of CLAC was found to be crucial for the interaction with A. These findings may be useful for future therapeutic interventions aimed at finding compounds that modulate the binding of CLAC to A deposits.

Received for publication, April 1, 2004 , and in revised form, October 25, 2004.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Karolinska Inst., Neurotec, Novum Kaspac Plan 5, SE-141 57 Huddinge, Sweden. Tel.: 46-8-585-836-21; Fax: 46-8-585-836-10; E-mail: linda.soderberg{at}neurotec.ki.se.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Osada, T. Hashimoto, A. Nishimura, Y. Matsuo, T. Wakabayashi, and T. Iwatsubo CLAC Binds to Amyloid {beta} Peptides through the Positively Charged Amino Acid Cluster within the Collagenous Domain 1 and Inhibits Formation of Amyloid Fibrils J. Biol. Chem., March 4, 2005; 280(9): 8596 - 8605. [Abstract] [Full Text] [PDF]